Clinical Trial Results:
A Phase 2b, Multicenter, Randomized, Open-label Study to Investigate the Efficacy, Safety and Pharmacokinetics of Different Treatment Regimens of AL-335, Odalasvir, and Simeprevir in Treatment-naive and Treatment-experienced Subjects With Chronic Hepatitis C Virus Genotype 1, 2, 4, 5 and 6 Infection Without Cirrhosis
Summary
|
|
EudraCT number |
2015-004200-38 |
Trial protocol |
DE BE PL IT |
Global end of trial date |
16 Nov 2017
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
31 Oct 2018
|
First version publication date |
31 Oct 2018
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
64294178HPC2001
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02765490 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Janssen-Cilag International NV
|
||
Sponsor organisation address |
Turnhoutseweg 30, Beerse, Belgium, B-2340
|
||
Public contact |
Clinical Registry Group, Janssen-Cilag International NV, ClinicalTrialsEU@its.jnj.com
|
||
Scientific contact |
Clinical Registry Group, Janssen-Cilag International NV, ClinicalTrialsEU@its.jnj.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
16 Nov 2017
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
16 Nov 2017
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
The main objective of this study was to evaluate the efficacy, that is, the sustained virologic response 12 weeks (SVR) after the end of the treatment (EOT) (SVR12) of a combination treatment with AL-335, odalasvir (ODV), and simeprevir (SMV) for 6 and 8 weeks in chronic hepatitis C virus (HCV) genotype 1, 2, 4, 5 or 6 infected subjects without cirrhosis.
|
||
Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. The safety assessments included Physical Examinations, Electrocardiograms
(ECG's), Echocardiography, Vital Signs (pulse/heart rate and blood pressure) and Clinical Laboratory Tests.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Nov 2016
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
6 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Belgium: 81
|
||
Country: Number of subjects enrolled |
Canada: 63
|
||
Country: Number of subjects enrolled |
Germany: 32
|
||
Country: Number of subjects enrolled |
Spain: 58
|
||
Country: Number of subjects enrolled |
Italy: 53
|
||
Country: Number of subjects enrolled |
Poland: 61
|
||
Country: Number of subjects enrolled |
Singapore: 17
|
||
Worldwide total number of subjects |
365
|
||
EEA total number of subjects |
285
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
342
|
||
From 65 to 84 years |
23
|
||
85 years and over |
0
|
|
|||||||||||||||||||
Recruitment
|
|||||||||||||||||||
Recruitment details |
- | ||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||
Screening details |
A total of 365 subjects (183 subjects in Arm A and 182 subjects in Arm B) were enrolled and treated in the study. Out of them 361 subjects (182 subjects in Arm A and 179 subjects in Arm B) completed the study. | ||||||||||||||||||
Period 1
|
|||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||
Arms
|
|||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||
Arm title
|
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks | ||||||||||||||||||
Arm description |
Subjects received AL-335 800 milligram (mg) (2*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
AL-335
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||
Dosage and administration details |
Subjects received AL-335 800 mg (2*400) tablets qd in the morning for 6 weeks.
|
||||||||||||||||||
Investigational medicinal product name |
Odalasvir
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||
Dosage and administration details |
Subjects received Odalasvir 25 mg tablet qd in the morning for 6 weeks.
|
||||||||||||||||||
Investigational medicinal product name |
Simeprevir
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Capsule
|
||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||
Dosage and administration details |
Subjects received Simeprevir 75 mg capsule qd in the morning for 6 weeks.
|
||||||||||||||||||
Arm title
|
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks | ||||||||||||||||||
Arm description |
Subjects received AL-335 800 mg (2*400) tablets, Odalasvir 25 mg tablet, and Simeprevir 75 mg capsule qd orally in the morning for 8 weeks. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
AL-335
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||
Dosage and administration details |
Subjects received AL-335 800 mg (2*400) tablets qd in the morning for 8 weeks.
|
||||||||||||||||||
Investigational medicinal product name |
Odalasvir
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||
Dosage and administration details |
Subjects received Odalasvir 25 mg tablet qd in the morning for 8 weeks.
|
||||||||||||||||||
Investigational medicinal product name |
Simeprevir
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Capsule
|
||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||
Dosage and administration details |
Subjects received Simeprevir 75 mg capsule qd in the morning for 8 weeks.
|
||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received AL-335 800 milligram (mg) (2*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received AL-335 800 mg (2*400) tablets, Odalasvir 25 mg tablet, and Simeprevir 75 mg capsule qd orally in the morning for 8 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
|
||
Reporting group description |
Subjects received AL-335 800 milligram (mg) (2*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks. | ||
Reporting group title |
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
|
||
Reporting group description |
Subjects received AL-335 800 mg (2*400) tablets, Odalasvir 25 mg tablet, and Simeprevir 75 mg capsule qd orally in the morning for 8 weeks. |
|
|||||||||||||
End point title |
Percentage of Subjects With Sustained Virologic Response 12 Weeks after End of Treatment (EOT) (SVR12) [1] | ||||||||||||
End point description |
The SVR 12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 12 weeks after actual EOT. Intent-To-Treat (ITT) population included all randomized subjects who took at least 1 dose of the study drug [that is AL-335, Odalasvir (ODV) or Simeprevir (SMV)].
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Week 12 (Follow-Up Phase)
|
||||||||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistical analysis was performed for this endpoint. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Subjects With Sustained Virologic Response 24 Weeks After End of Treatment (SVR24) | ||||||||||||
End point description |
The SVR24 was defined as HCV RNA <LLOQ (detectable or undetectable) 24 weeks after End of Treatment (EOT). ITT population included all randomized subjects who took at least 1 dose of the study drug (i.e., AL-335, ODV or SMV). Last Observation Carried Forward (LOCF) method was used to impute the missing values.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24 (Follow-Up Phase)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Number of Subjects With Viral Relapse | |||||||||
End point description |
Viral Relapse: Subjects who did not achieve SVR12, with HCV RNA <LLOQ at the EOT and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow-up. ITT population included all randomized subjects who took at least 1 dose of the study drug (i.e., AL-335, ODV or SMV).
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
End of Treatment up to Week 24 (Follow up phase)
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Number of Subjects With Late Viral Relapse | |||||||||
End point description |
Late Viral Relapse: Subjects who achieved SVR12 but had confirmed HCV RNA >=LLOQ afterwards during follow-up. ITT population included all randomized subjects who took at least 1 dose of the study drug (i.e., AL-335, ODV or SMV).
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to Week 24 (Follow-up Phase)
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Subjects With On-treatment Failure | ||||||||||||
End point description |
On-treatment failure: Subjects who did not achieve SVR12 and with confirmed HCV RNA>=LLOQ at the End of Treatment (EOT). ITT population included all randomized subjects who took at least 1 dose of the study drug (i.e., AL-335, ODV or SMV).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
EOT up to Week 12 (Follow up Phase)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Subjects With Sustained Virologic Response 4 Weeks after End of Treatment (EOT) | ||||||||||||
End point description |
The SVR 4 was defined as subjects who were considered to reach SVR4, if 4 weeks after the actual EOT, HCV RNA was <LLOQ (detectable or undetectable). ITT population included all randomized subjects who took at least 1 dose of the study drug (i.e., AL-335, ODV or SMV).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 4 (Follow-Up Phase)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Screening up to Follow-up (Week 24)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received AL-335 800 milligram (mg) (2*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received AL-335 800 mg (2*400) tablets, Odalasvir 25 mg tablet, and Simeprevir 75 mg capsule qd orally in the morning for 8 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
17 Jun 2016 |
The overall reason for the amendment is to change in design of the Phase 2b study with focus on evaluating the 3 Direct-Acting Antiviral Agent (DAA) treatment regimen comprising of AL-335+Odalasvir (ODV) with Simeprevir (SMV). |
||
12 Aug 2016 |
The overall reason for the amendment is to change in design of the Phase 2b study with focus on treatment-naive and treatment-experienced hepatitis C virus (HCV) genotype 1, 2, 4, 5 or 6 infected subjects without cirrhosis. |
||
10 Apr 2017 |
The overall reason for the amendment is to implement study treatment stopping rules upon Health Authority feedback. In addition, as more subjects have been recruited than originally planned for, the actual number of subjects enrolled in the study is added and statistical considerations for safety are adjusted accordingly. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |